Hypersomnia affects approximately 5% of the population and can burden affected individuals by, e.g., interfering with the ability to operate motor vehicles, socialize or maintain employment. It is a disorder characterized by excessive daytime sleepiness (EDS). Broadly classified, there are primary and secondary hypersomnias. Primary hypersomnias are believed to result from problems with an individual's brain functions that regulate sleep and wake. Primary hypersomnias are thought to occur independent of other underlying diseases or conditions. Secondary hypersomnias are believed to be caused by problems with night-time sleep, inability to get enough sleep or other medical problems that result in sleepiness, including, e.g., infections, depression, kidney failure, chronic fatigue syndrome, and neurodegenerative diseases such as Parkinson's disease and myotonic dystrophy. More specific classifications of hypersomnia include, e.g., the International Classification of Sleep Disorders—Second Edition (ICSD-2) (American Academy of Sleep Medicine, Westchester Ill. 2005) and the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) (American Psychiatric Association, Washington D.C. 2013). Other publications describing clinical features of hypersomnia are, e.g., Ali et al., 2009, J. Clin. Sleep Med. 5, 562-568; Harris et al., 2012, Neurol. Clin. 30, 1027-1044.
Not much is known about the pathophysiology underlying primary hypersomnia. Researchers have suggested that, among other things, injury to adrenergic neurons or that decreased histamine levels may be associated with primary hypersomnia. See, e.g., Montplaisir et al., 1982, Neurology 32(11), 1299-302; Kanbayashi et al., 2009, Sleep 32(2), 181-7; Harris et al., 2012, Neurol Clin 30, 1027-104. Others have linked primary hypersomnia to an endogenous enhancement of type A gamma-aminobutyric acid (GABAA) receptor activity in hypersomnia patients. See, e.g., Rye et al., 2012, Sci. Tansl. Med. 4, 161ra151 (pages 1-10); Trotti, et al., 2013, J. Psychopharmacol. 0269881113515062 [online publication], Kelty et al., 2014, J. Psychopharmacol., 0269881114523865 [online publication].
Treatments for primary hypersomnia include stimulants and wake-promoting agents such as caffeine, amphetamines, modafinil, and armodafinil. See, e.g., Ali et al., 2009, J. Clin. Sleep Med. 5, 562-568; Harris et al., 2012, Neurol Clin 30, 1027-104. Potential treatments for GABA-related hypersomnia have been described in publications such as Parker et al., U.S. Patent Application Publication No. US 2011/0028418 A1, published Feb. 3, 2011; Trotti, et al., 2013, J. Psychopharmacol. 0269881113515062 [online publication], Kelty et al., 2014, J. Psychopharmacol., 0269881114523865 [online publication].
Treatments for hypersomnia that can, e.g., be orally administered, lack undesirable side-effects or are not habit-forming when taken, are desired.